What is AMPK?

AMPK (5′ AMP-activated protein kinase) is an enzyme that plays a key role in energy balance. All creatures from yeast to humans have this enzyme (R).

AMPK can detect the level of energy (number of ATP molecules) in a cell and helps regulate responses when it gets too low or high.

AMPK is produced in a number of tissues, including the liver, brain, fat cells and muscle (R).

While much of AMPK activity is dependent on external factors such as diet and exercise we all have a genetic disposition inherited from our parents.

To learn more about how you can have your own genetic makeup analyzed for AMPK related factors go to SelfDecode.

AMPK Activation Benefits

1) AMPK Increases Metabolism

AMPK in the hypothalamus senses our level of energy production in the body (energy in the form of ATP). It increases energy expenditure and can also increase appetite (when increased in the hypothalamus) (R).

When cellular energy is low, AMPK is activated and targets a range of processes, the net response of which is an increase in energy production and a coordinated decrease in energy (ATP) usage (R).

2) AMPK Produces and Burns Sugars

Glucose is the main source of energy for the body and is particularly essential for normal brain activity. Hypoglycemia, a condition in which the blood glucose drops below normal levels, poses a great danger to the stability and functioning of the brain and therefore activates AMPK (R).

Hypothalamic AMPK activation promotes glucose production from the liver (R), and glucose uptake into the muscles (R).

3) AMPK Burns Fat

4) AMPK Inhibits Protein Production

Protein production is a high-energy process that is inhibited during low energy states to conserve energy. Therefore, it is not surprising that AMPK inhibits protein production (R).

Inhibiting excessive protein production results in a much more energy efficient and wasteful cell.

5) AMPK Promotes Cellular Renewal (Autophagy)

Autophagy is the process of recycling cellular components. This process promotes molecular and cell subunit quality control by degrading damaged or misfolded proteins and even damaged mitochondria (R).

Autophagy can contribute to energy generation by providing fuel for mitochondrial metabolism, and AMPK promotes this process (R).

6) AMPK Produces New Mitochondria

AMPK is capable of both acute and long-term improvement of mitochondrial activity (R).

AMPK also controls the production and turnover of mitochondria. Loss of AMPK in mice reduces mitochondrial activity and greatly diminishes muscle performance (R).

8) AMPK Helps With Oxygen Delivery

Upon hypoxia (low oxygen) at altitude or during sleep, activation of AMPK can protect against acute breathing instability. Loss of AMPK was shown to cause breathing dysfunction during hypoxia in mice (R).

Variations of gene components of AMPK has been found in high-altitude Andean populations, presumably in order to help survival in low oxygen conditions (R,R).

9) AMPK is Important for Fertility

AMPK helps with fertility in both sexes in several animal species, by increasing the production of sex hormones (R).

10) AMPK Increases Blood Flow

AMPK plays a critical role in increasing blood flow through vasodilation (widening of the blood vessels), by stimulating nitric oxide release in blood vessels (R).

11) AMPK Provides the Benefits of Exercise

The benefits of exercise can be obtained, in part, by activating AMPK. Mice who took AICAR, an AMPK activator, for 4 weeks had the similar benefits as endurance training in “sedentary” mice (in terms of both muscle mitochondrial profiles and actual treadmill endurance) (R).

12) AMPK Increases Weightloss

AMPK increases ‘fat burning’ and this ‘pathway’ can result in weight loss(R).

For weight loss, ideally, we would want to activate AMPK in our liver, fat, and muscle and inhibit AMPK in the hypothalamus. This way, we will burn fat and energy stores and decrease hunger at the same time.

In mice, when the activity of brain/hypothalamic AMPK was inhibited, the mice ate less and lost weight. When AMPK activity was raised the mice ate more and gained weight (R).

16) AMPK Benefits the Heart

17) AMPK Increases Testosterone

AMPK can increase male hormones/androgens in human cells (R). However, metformin (AMPK activator) is commonly given to women with PCOS to a good effect (PCOS is a condition with higher male hormones).

Negatives of AMPK

AMPK can suppress PPAR alpha and PPAR gamma (R), two important proteins that have beneficial functions in the body.

AMPK May Help or Hurt These Conditions

AMPK and Neurodegenerative Disease

AMPK has both protective and contributing properties when it comes to neurodegenerative diseases, and studies often come to opposing conclusions regarding this enzyme and its role.

In mice with Alzheimer’s, activation of AMPK by metformin was shown to increase amyloid-beta protein (Aβ) levels and therefore contribute to the disease (R).

However, Aβ generation was also shown to be increased in AMPK deficient mice (R). Furthermore, AMPK activation by resveratrol and AICAR also decreased Aβ secretion (R).

Indeed, the inactivation of AMPK was linked to increased Alzheimer’s risk in obese patients with type 2 diabetes (R).

In mice with Huntington’s disease, AMPK activation promoted neuronal loss and brain decay (R). But then again, another study showed that treatment with metformin significantly prolonged survival time in rodents with this disease (R).

Genetic activation of AMPK was also shown to protect against neuronal loss in Parkinson’s disease models in flies (R).

On the other hand, AMPK promotes glucose/energy uptake by cells, which can also be used by tumors once they have formed (R).

Given the above, it is suggested that AMPK activation is beneficial for cancer prevention but not for cancer treatment. Rather, AMPK inhibition could be useful for treating established cancers by inhibiting tumor stress adaptation and survival (R).

AMPK activation by its activators (AICAR and metformin) increased UVB-induced DNA repair in normal human skin cells. Topical treatment with AICAR and metformin not only delayed the onset of UVB-induced skin tumor formation but also reduced the number of tumors in mice (R).

Top 5 Ways to Increase AMPK Naturally

We want to increase AMPK in our muscle, fat, and liver cells and decrease it in our hypothalamus (if you have weight issues).

1) Exercise

Exercise uses energy (in the form of ATP), and the resulting lack of energy stimulates AMPK (R).

Many beneficial effects of exercise are carried out through AMPK, such as the insulin-sensitizing effect (R).

Through its effect on increasing the production of new mitochondria, AMPK can improve muscle performance.

The World Anti-Doping Agency (WADA) banned the AMPK activator AICAR because of its performance-enhancing effects (R).

2) Calorie Restriction

It is known that calorie restriction exerts many beneficial effects on aging, diabetes, and cancer. Some of these effects are mediated by AMPK. It was shown that calorie restriction activates AMPK through multiple mechanisms (R).

Ginseng/Ginsenosides. A number of ginsenosides have been reported to activate AMPK, resulting in an increased glucose uptake, decreased liver triglyceride and cholesterol levels, and the inhibition of fat production and liver glucose production (R).

Hormones/Pathways that Activate AMPK (in liver, fat, and muscle)

1) Adiponectin

In fasting, adiponectin increases and stimulates AMPK, leading to induction of food intake and reduction of energy expenditure. After refeeding, a decrease in adiponectin level is accompanied by blunted AMPK activity (R).

2) Leptin

Leptin, the satiety and anti-obesity hormone secreted by fat cells in the presence of insulin, prevents overeating by inhibiting AMPK in the hypothalamus to suppress appetite (R) but activates AMPK in muscle (R).

3) Thyroid hormone T3

4) Nitric Oxide

5) ROS-producing agents

Any modulators capable of inducing intracellular reactive oxygen species (ROS) generation can activate AMPK. Such a modulator is cryptotanshinone from red sage (Salvia miltiorrhiza), which exerts antidiabetic and anticancer effects through ROS-dependent AMPK activation. DNA-damaging agents, such as cisplatin or metals, including arsenite, vanadate, and cobalt, also activate AMPK through ROS generation (R).

Drugs that Activate AMPK

1) Metformin

Metformin is a blood-sugar-lowering agent. It is widely used for the treatment of type 2 diabetes (R).

AMPK mediates many of the antidiabetic actions of metformin: stimulation of fat burning and glucose uptake, and decreased fat production and liver glucose production (R).

2) Aspirin

Aspirin reduces circulating free fatty acids and TG levels in obese patients with type-2 diabetes and increases fat breakdown during fasting in healthy humans, which can be explained by the direct effect of aspirin on AMPK activation (R).

3) Thiazolidinediones

Thiazolidinediones act primarily by activating PPARγ. However, they also exert their antidiabetic effect in part through AMPK activation (R).

Thiazolidinediones rapidly activate AMPK in a variety of tissues including muscle, liver, and fat tissue (R).

AMPK has been implicated in the TZDs induced body weight gain. TZDs are prescribed for blood sugar control but induce body weight gain as a side effect. Pioglitazone treatment was reported to increase food intake and decrease energy expenditure by enhancing adiponectin and increasing the AMPK activity in the hypothalamus (R).

Hormones That Activate AMPK in the Hypothalamus

1) Ghrelin

Ghrelin is a hunger hormone produced in the stomach and released during fasting. Ghrelin is essential for survival during severe calorie restriction or fasting when it maintains blood glucose levels (R).

Ghrelin activates AMPK in the hypothalamus and stimulates food intake (R), however, it inhibits AMPK in the fat tissue and liver (R).

2) Cannabinoids

Cannabinoids stimulate AMPK activity in the hypothalamus leading to increased appetite (R). However, it decreases AMPK in fat cells and liver, similar to Ghrelin (R).

AMPK activation results in the reduction of mTOR. But you can have scenarios where both AMPK is activated and mTOR is also activated because AMPK doesn’t inhibit it directly; it inhibits another protein that directly increases mTOR. For example, Ghrelin, the hunger hormone, activates AMPK and mTOR in the hypothalamus (R).

Disclaimer and Caveats

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JOE COHEN

CEO, SelfHacked

About Joe

Growing up, Joe was plagued with a myriad of health issues such as gut problems, autoimmune issues, chronic fatigue, brain fog, insomnia, and general inflammation. Both conventional and alternative doctors weren’t able to help him, so he decided to fix himself. With lots of health questions and few satisfying answers, Joe decided to read every research paper he could get his hands on and conduct thousands of experiments on his own body in order to fix his health issues. Joe started SelfHacked in late 2013 when he successfully fixed all of his issues, and now it gets millions of readers a month looking to educate themselves about how they can improve their health. Joe is now a thriving author, speaker, and serial entrepreneur, founding SelfDecode & LabTestAnalyzer.

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